Dynamic induction of the myelin-associated growth inhibitor Nogo-A in perilesional plasticity regions after human spinal cord injury

Brain Pathology, 2023 · DOI: 10.1111/bpa.13098 · Published: January 1, 2023

Spinal Cord Injury Neurology Neuroplasticity

Simple Explanation

Spinal cord injury (SCI) can lead to lifelong disability by damaging sensory and motor functions. Recovery depends on factors like the initial injury extent and progressive demyelination. Nogo-A, a protein expressed by oligodendrocytes and motoneurons, inhibits axonal growth and sprouting after SCI. Blocking Nogo-A is considered a therapeutic strategy to enhance neuroaxonal plasticity and repair. This study investigates Nogo-A expression in spinal cord lesions and surrounding areas after SCI, assessing its role in inhibiting neuroaxonal plasticity. The study specifically looks at the spinal lesion core and perilesional rim.

Study Duration

1.5 years

Participants

22 SCI subjects and 9 controls

Evidence Level

Not specified

Key Findings

1
Nogo-A expression is dominated by TPPP/p25+ oligodendrocytes after SCI.
2
Nogo-A+/TPPP/p25+ oligodendrocytes increased over time after SCI in the perilesional rim, reaching peak levels at chronic SCI stages.
3
Numbers of Nogo-A+/TPPP/p25+ oligodendrocytes at the lesion core only fluctuated, with a decline observed between stages III and IV.

Research Summary

This study examined Nogo-A expression in human spinal cord injury (SCI) at the lesion core and perilesional rim, focusing on its role in plasticity and axonal damage. The research compared spinal cord specimens from SCI subjects (n = 22) to controls (n = 9) across acute to chronic stages after SCI. The study found that Nogo-A expression is primarily in TPPP/p25+ oligodendrocytes and increases over time in the perilesional rim, peaking at chronic stages. This suggests an extended therapeutic window for anti-Nogo-A pathway targeting interventions beyond 4 weeks post-SCI. In contrast, Nogo-A expression at the lesion core fluctuated and declined in later stages, indicating differential regulation of Nogo-A in these regions. This dynamic expression suggests a contribution to maintaining an environment hostile to neuroaxonal plasticity after human SCI.

Practical Implications

Extended Therapeutic Window

The findings suggest that anti-Nogo-A therapies may be effective even in chronic SCI patients, expanding the treatment window beyond the initial 4 weeks.

Targeted Therapies

Future research should investigate combining anti-Nogo-A therapy with biomaterials or scar-degrading enzymes to overcome barriers in chronic SCI.

Plasticity Enhancement

Understanding the role of Nogo-A in inhibiting neuroaxonal plasticity can lead to better strategies for promoting recovery-related networks after SCI.

Study Limitations

1
The study used formalin-fixed paraffin-embedded tissue, limiting additional analyses like western blotting.
2
Quantification of proliferation was limited in postmortem tissue.
3
The study included a heterogeneous group of injury types, stages after SCI, and age, with a small study population overall and in respective groups.

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